GPD1L在肾透明细胞癌中的表达及其临床意义

Expression and clinical significance of GPD1L in clear cell renal carcinoma

目的分析甘油磷酸脱氢酶1样抗原(GPD1L)在肾透明细胞癌中的表达及其临床意义。方法选用包含79例肾透明细胞癌及10例肾脏正常组织的组织芯片,使用免疫组织化学染色法(免疫组化)检测GPD1L蛋白的表达情况,并运用癌症基因组图谱(TCGA)数据库收集包含GPD1L mRNA资料的肾透明细胞癌患者相关资料。观察组织芯片中肾脏正常组织与肾透明细胞癌组织GPD1L蛋白的表达部位及表达强度,分析TCGA中肾脏正常组织与肾透明细胞癌组织GPD1L基因的表达水平差异。按基因芯片或TCGA中肾透明细胞癌GPD1L蛋白或mRNA表达情况分为高表达组与低表达组,分析肾透明细胞癌患者GDP1L蛋白或mRNA表达与临床特征及总体生存期(OS)的关系。应用单因素和多因素Cox比例风险回归分析肾透明细胞癌患者OS的影响因素。结果组织芯片中,GPD1L蛋白阳性染色呈棕黄色或褐色,在肾透明癌细胞与肾脏正常组织中主要表达于肾小管上皮的细胞胞质中,GPD1L蛋白在肾透明细胞癌组织表达强度低于其在正常肾脏组织中的表达强度(P<0.001),GPD1L蛋白低表达组中病理分级高和临床分期晚者比例高于高表达组(P均<0.05)。TCGA中,肾透明细胞癌组织GPD1L mRNA表达水平低于肾脏正常组织(P<0.05),GPD1L mRNA低表达组中女性、病理分级高、临床分期晚、有转移、死亡者比例均高于高表达者(P均<0.05), GPD1L mRNA低表达组OS低于高表达组(P<0.001)。Cox比例风险回归分析显示,GPD1L mRNA表达水平、年龄、肿瘤转移为肾透明细胞癌OS的影响因素(P均<0.05)。结论 GPD1L的表达与肾透明细胞癌密切相关,可考虑作为临床诊断及预后的分子标志物。

Objective To investigate the expression and clinical significance of GPD1 L(glycerol-3-phophate dehydrogenase 1 like) in clear cell renal carcinoma.Methods Tissue microarrays including 79 cases of clear cell renal carcinoma and 10 cases of normal tissuess were selected.The expression level of GPD1 L protein was detected by immunohistochemistry.Relevant data including GPD1 L mRNA data of patients were collected by the TCGA database.The expression location and intensity of GPD1 L protein were quantitatively analyzed between two groups.The expression level of GPD1 L mRNA was statistically compared between two groups in TCGA database.According to the expression levels of GPD1 L protein and mRNA in the microarray or TCGA database,all patients were assigned into the high and low expression groups.The correlation between the expression of GPD1 L mRNA,clinical features and overall survival(OS) was analyzed.The influencing factors of OS were identified by univariate and multivariate Cox’s proportional hazard regression analyses.Results In the tissue microarray,GPD1 L protein was positively stained as yellow brown or brown,mainly expressed in the cell cytoplasm of the renal tubular epithelium of the clear cell renal carcinoma and normal renal tissues.The expression intensity of GPD1 L protein in the clear cell renal carcinoma was significantly lower than that in normal renal tissues(P<0.001).The proportion of patients with high grade and late clinical stage in the low expression of GPD1 L protein group was significantly higher compared with that in the high expression group(both P<0.05).In TCGA database,the expression level of GPD1 L mRNA in the clear cell renal carcinoma tissues was remarkably lower than that in the normal renal tissues(P<0.05).In the low expression of GPD1 L mRNA group,the proportion of female patients,those with high pathological grade,high clinical stage,metastasis and death was significantly higher compared with those in the high expression group(all P<0.05).In addition,the OS in the low expression group was significantly shorter than that in the high expression group(P<0.001).Cox’s proportional hazard regression analysis demonstrated that the expression level of GPD1 L mRNA,age and tumor metastasis were the influencing factors of the OS of patients(all P<0.05)Conclusion The expression of GPD1 L is intimately correlated with clear cell renal carcinoma,which can be considered as a molecular marker for clinical diagnosis and prognosis.